Metastasis of aggressive breast cancer is a devastating and ultimately fatal condition. The current first- line agents which are used to treat breast cancer metastasis primarily target tumor growth. These drugs produce only modest increases in survival in patients with aggressive metastatic cancers and have significant side effects. Currently, there are no available treatment options that can specifically and effectively inhibit tumor invasion and metastasis. Therefore, novel drug strategies are needed to treat this chronic, fatal and incurable condition. Our therapeutic strategy for the treatment of aggressive breast cancer is based on reducing Id-1 expression. Id-1 is a key regulator of the invasive and metastatic potential of breast and additional cancers. In this Phase I proposal our focus will be on the optimization of our lead compound to discover one or more analogs that down-regulate Id-1 expression and consequently inhibit breast cancer cell invasion and metastasis. We will also optimize these compounds so that they display a favorable ADME-Tox profile. The ultimate goal of this proposal is to develop a novel therapeutic approach for the treatment of metastatic human breast cancers by down-regulation of Id-1.